Codeine Phosphate Hemihydrate. Tablet: Solpadol Caplets are white capsule shaped tablets, marked SOLPADOL on one side.

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT Solpadol Caplets Solpadol Capsules Solpadol 30mg/500mg Effervescent Tablets 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Active Constituents Paracetamol Codeine Phosphate Hemihydrate 500.0mg 30.0mg For excipients see PHARMACEUTICAL FORM Tablet: Solpadol Caplets are white capsule shaped tablets, marked SOLPADOL on one side. Capsule: Solpadol Capsules are grey and purple with SOLPADOL printed on them in black ink. Effervescent Tablets: Solpadol Effervescent Tablets are white bevelled-edge tablets scored on one face. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications For the relief of severe pain. 4.2 Posology and method of administration Adults: Elderly: Children: Two tablets not more frequently than every 4 hours, up to a maximum of 8 tablets in any 24 hour period. As adults, however a reduced dose may be required. See warnings. Not recommended for children under 12 years of age. Solpadol Caplets, Capsules and Effervescent Tablets are for oral administration. 4.3 Contraindications Hypersensitivity to paracetamol or codeine which is rare.

2 Hypersensitivity to any of the other constituents. Conditions where morphine and opioids are contraindicated e.g: Acute asthma Respiratory depression Acute alcoholism Head injuries Raised intra-cranial pressure Following biliary tract surgery Monoamine oxidase inhibitor therapy, concurrent or within 14 days. 4.4 Special warnings and precautions for use Each tablet of the soluble formulation contains 388mg sodium (16.87m Equivalents). This sodium content should be taken into account when prescribing for patients in whom sodium restriction is indicated. As the effervescent tablet contains sorbitol, patients with rare hereditary problems of fructose intolerance should not take this medicine. Care should be observed in administering the product to any patient whose condition may be exacerbated by opioids, particularly the elderly, who may be sensitive to their central and gastro-intestinal effects, those on concurrent CNS depressant drugs, those with prostatic hypertrophy and those with inflammatory or obstructive bowel disorders. Care should also be observed if prolonged therapy is contemplated. Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with alcoholic liver disease. Patients should be advised not to exceed the recommended dose and not take other paracetamol containing products concurrently. Patients should be advised to consult a doctor should symptoms persist and to keep the product out of the reach and sight of children. The risk-benefit of continued use should be assessed regularly by the prescriber. The leaflet will state in a prominent position in the before taking section: Do not take for longer than directed by your prescriber. Taking codeine regularly for a long time can lead to addiction, which might cause you to feel restless and irritable when you stop the tablets. Taking a pain killer for headaches too often or for too long can make them worse. The label will state (To be displayed prominently on outer pack (not boxed) :

3 Do not take for longer than directed by your prescriber as taking codeine regularly for a long time can lead to addiction. 4.5 Interaction with other medicinal products and other forms of interaction Paracetamol may increase the elimination half-life of chloramphenicol. Oral contraceptives may increase its rate of clearance. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect. The effects of CNS depressants (including alcohol) may be potentiated by codeine. 4.6 Pregnancy and lactation There is inadequate evidence of the safety of codeine in human pregnancy, but there is epidemiological evidence for the safety of paracetamol. Both substances have been used for many years without apparent ill consequences and animal studies have not shown any hazard. Nonetheless careful consideration should be given before prescribing the products for pregnant patients. Opioid analgesics may depress neonatal respiration and cause withdrawal effects in neonates of dependent mothers. Paracetamol is excreted in breast milk but not in a clinically significant amount. 4.7 Effects on ability to drive and use machines Patients should be advised not to drive or operate machinery if affected by dizziness or sedation. 4.8 Undesirable effects Codeine can produce typical opioid effects including constipation, nausea, vomiting, dizziness, light-headedness, confusion, drowsiness and urinary retention. The frequency and severity are determined by dosage, duration of treatment and individual sensitivity. Tolerance and dependence can occur, especially with prolonged high dosage of codeine. Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

4 Regular prolonged use of codeine/dhc is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is then stopped. Prolonged use of a painkiller for headaches can make them worse. Very rare occurrence of pancreatitis. 4.9 Overdose Codeine The effects of Codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs. Symptoms Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been coingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely. Management Management should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg. Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least 4 hours after ingestion, or 8 hours if a sustained release preparation has been taken. Paracetamol Patients in whom oxidative liver enzymes have been induced, including alcoholics and those receiving barbiturates and patients who are chronically malnourished, may be particularly sensitive to the toxic effects of paracetamol in overdose. Symptoms Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Liver damage is likely in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately

5 detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue. Management Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested around 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N- acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available. 5 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Anilides, Paracetamol combinations ATC Code: NO2B E51 Paracetamol is an analgesic which acts peripherally, probably by blocking impulse generation at the bradykinin sensitive chemo-receptors which evoke pain. Although it is a prostaglandin synthetase inhibitor, the synthetase system in the CNS rather than the periphery appears to be more sensitive to it. This may explain paracetamol's lack of appreciable anti-inflammatory activity. Paracetamol also exhibits antipyretic activity. Codeine is a centrally acting analgesic which produces its effect by its action at opioid-binding sites (m-receptors) within the CNS. It is a full agonist. 5.2 Pharmacokinetic properties The bioavailabilities of paracetamol and codeine phosphate when given as the combination are similar to those when they are given separately. Caplets Following oral administration of two tablets (ie, a dose of paracetamol 1000mg and codeine 60mg) the mean maximum plasma concentrations of paracetamol and codeine were 15.96mg/ml and 212.4ng/ml respectively. The mean times to maximum plasma concentrations were 0.88 hours for paracetamol and 1.05 hours for codeine. The mean AUC for the 9 hours following administration was 49.05µg/ml per hour for paracetamol and 885.0ng/ml per hour for codeine. Capsules Following oral administration of two capsules (ie, a dose of paracetamol 1000mg and codeine phosphate 60mg) the mean maximum plasma concentrations of paracetamol and codeine phosphate were 17.5 µg/ml and 327ng/ml respectively.

6 The mean times to maximum plasma concentrations were 1.03 hours for paracetamol and 1.10 hours for codeine phosphate. The mean AUC(0-10) following administration was 48.0µg/ml per hour for paracetamol and 1301ng/ml per hour for codeine. Effervescent tablets Following oral administration of two effervescent tablets (i.e., a dose of paracetamol 1000mg and codeine 60mg) the mean maximum plasma concentrations of paracetamol and codeine were 20.4µg/ml and 218.8ng/ml respectively. The mean times to maximum plasma concentrations were 0.34 hours for paracetamol and 0.42 hours for codeine phosphate. The mean AUC for the 10 hours following administration was 50.0µg/ml per hour for paracetamol and 450.0ng/ml per hour for codeine. 5.3 Preclinical safety data Caplets & Effervescent Tablets: There are no preclinical data of relevance which are additional to that already included in other sections of the SPC. Capsules: None stated 6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients Solpadol Caplets: Pregelatinised starch, Maize starch, Povidone, Potassium sorbate, Microcrystalline cellulose, Stearic acid, Talc, Magnesium stearate, Croscarmellose sodium (type A). Solpadol Capsules: Maize starch, Magnesium stearate, Talc, Indigotine E132, Azorubine E122, Titanium dioxide E171, Gelatin, Black iron oxide E172, Shellac, Propylene glycol Solpadol Effervescent: Sodium bicarbonate, Anhydrous citric acid, Anhydrous sodium carbonate, Sorbitol powder, Saccharin sodium, Povidone, Dimeticone, Sodium lauril sulfate. 6.2 Incompatibilities None known. 6.3 Shelf life Caplets: 5 years. Capsules: 3 years Effervescent: 4 years

7 6.4 Special precautions for storage Caplets and Capsules: Store in the original package. Do not store above 25 C. Effervescent: Do not store above 25 C. 6.5 Nature and contents of container Caplets: PVC/aluminium foil (250µm/20µm) / PVC (15µm) blister packs. Pack sizes: 30 and 100 tablets. Capsules: White, opaque PVC (250µm)/aluminium foil (20µm)/ PVC (15µm) blister packs or White, opaque PVC (250µm)/ 35gsm Glassine (Pergamin) paper/9µm soft temper Aluminium foil contained in cardboard cartons. Pack sizes of 100 capsules. Effervescent: PPFP strips in cardboard containers. Pack sizes: 32 and 100 tablets. 6.6 Special precautions for disposal Capsules and caplets: no special requirements. Solpadol Effervescent Tablets should be dissolved in half a tumberful of water before taking. 7 MARKETING AUTHORISATION HOLDER Sanofi-aventis One Onslow Street Guildford Surrey GU1 4YS UK 8 MARKETING AUTHORISATION NUMBER(S) Caplets: PL 04425/0637 Capsules: PL 04425/0635 Effervescent: PL 04425/ DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 4th December DATE OF REVISION OF THE TEXT Caplets and capsules: 26 November 2009 Effervescent: 1 March 2010

8 Legal category: POM